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建立液相色谱-串联质谱法同时测定血浆和尿液中色氨酸及犬尿氨酸途径 10 种关键代谢产物的方法学验证:在急性肾损伤患者队列中的应用。

Validation of a liquid chromatography coupled to tandem mass spectrometry method for simultaneous quantification of tryptophan and 10 key metabolites of the kynurenine pathway in plasma and urine: Application to a cohort of acute kidney injury patients.

机构信息

Department of Clinical Chemistry, Georges Pompidou European Hospital, AP-HP, 20 rue Leblanc, 75015 Paris, France; Paris University, INSERM UMRS1138, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de médecine, 75006 Paris, France.

Department of Clinical Chemistry, Georges Pompidou European Hospital, AP-HP, 20 rue Leblanc, 75015 Paris, France.

出版信息

Clin Chim Acta. 2022 Sep 1;534:115-127. doi: 10.1016/j.cca.2022.07.009. Epub 2022 Jul 20.

DOI:10.1016/j.cca.2022.07.009
PMID:35870540
Abstract

A sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of tryptophan (Trp) and ten metabolites of kynurenine pathway, including kynurenine (Kyn), 3-hydroxy-kynurenine (3-HK), kynurenic acid (KA), xanthurenic acid (XA), 3-Hydroxy-anthranilic acid (3-HANA), quinolinic acid (QA), nicotinic acid mononucleotide (NaMN), picolinic acid (Pic), nicotinamide (NAM) and nicotinic acid (NA) in both plasma and urine. This LC-MS/MS method was used to predict the occurrence of acute kidney injury (AKI) in a cohort of patients with cardiac surgery under cardiopulmonary bypass (CPB). Urinary concentrations of Pic, as well as Pic to Trp and Pic to 3-HANA ratios were highly predictive of an AKI episode the week after CPB, indicating that Pic could be a predictive biomarker of AKI. Thus, monitoring the kynurenine pathway activity with this LC-MS/MS method is a clinically relevant tool to identify new biomarkers of kidney injury.

摘要

建立并验证了一种灵敏、快速的液相色谱-串联质谱(LC-MS/MS)法,用于同时测定色氨酸(Trp)和犬尿氨酸途径的十种代谢物,包括犬尿氨酸(Kyn)、3-羟基犬尿氨酸(3-HK)、犬尿喹啉酸(KA)、黄尿酸(XA)、3-羟基邻氨基苯甲酸(3-HANA)、喹啉酸(QA)、烟酰胺单核苷酸(NaMN)、吡啶酸(Pic)、烟酰胺(NAM)和烟酸(NA),分别用于检测血浆和尿液。该 LC-MS/MS 方法用于预测体外循环(CPB)下心内直视手术后患者发生急性肾损伤(AKI)的情况。CPB 后一周,尿液中 Pic 浓度以及 Pic 与 Trp 比值、Pic 与 3-HANA 比值与 AKI 发作高度相关,提示 Pic 可能是 AKI 的预测性生物标志物。因此,使用这种 LC-MS/MS 方法监测犬尿氨酸途径的活性是一种具有临床相关性的工具,可以识别新的肾损伤生物标志物。

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